Sex-related differences in oxidative stress and neurodegeneration

Abstract

Oxidative stress has been implicated in a number of neurodegenerative diseases spanning various fields of research. Reactive oxygen species can be beneficial or harmful, depending on their concentration. High levels of reactive oxygen species can lead to oxidative stress, which is an imbalance between free radicals and antioxidants. Increased oxidative stress can result in cell loss. Interestingly, sex differences have been observed in oxidative stress generation, which may underlie sex differences observed in neurodegenerative disorders. An enhanced knowledge of the role of sex hormones on oxidative stress signaling and cell loss can yield valuable information, leading to sex-based mechanistic approaches to neurodegeneration.

Keywords: Aging; Alzheimer’s disease; Estrogen; Menopause; Parkinson’s disease; Testosterone.

Figure 1

Homocysteine levels (oxidative stress) increased with age in cognitively intact participants, regardless of sex. A significant regression equation was found (F (2, 248) = 3.821, p < 0.05), with an R² of 0.030. TARCC participants’ homocysteine levels are equal to 7.455 + 0.086 (age) − 0.495 (sex), where age is measured in years and sex is coded as men and women. Cognitively intact participants’ homocysteine levels increased 0.086 umol/L for every year and men had higher (0.495 umol/L) homocysteine (non-significant) than women. Only age was a significant predictor of homocysteine levels. Specific methods for sample collection are available in our prior publication [26]. Serum total homocysteine was assayed in the Atherosclerosis Clinical Research Laboratory at Baylor College of Medicine.

Figure 2

Homocysteine levels increased with age in both men and women with AD, with men have significantly higher homocysteine levels (oxidative stress) than women. A linear regression was calculated to homocysteine levels based on age and sex. A significant regression equation was found (F (2, 95) = 11.220, p < 0.05), with an R² of 0.191. TARCC participants’ homocysteine levels are equal to -5.525 + 0.348 (age) − 3.788 (sex), where age is measured in years and sex is coded as men and women. AD participants’ homocysteine levels increased 0.348 umol/L for every year and men had higher (3.788 umol/L) homocysteine than women. Both age and sex were significant predictors of homocysteine levels.